Cell Injury Flashcards
Cell injury
All cells have effective mechanisms to deal with mild changes in environmental conditions.
More severe changes in environment lead to cell adaptation, injury or cell death.
Degree of injury depends on: -
What causes cell injury?
Hypoxia
Toxins
Physical agents - Direct trauma
Hypoxia
Hypoxia versus ischaemia
Causes of hypoxia:
hypoxaemia hypoxia - arterial content of oxygen is low (occurs with reduced inspired pO2 at altitude and reduced absorption secondary to lung disease
anaemia hypoxia - decreased ability of Hb to carry oxygen (anaemia and CO poisoning)
Ischaemic hypoxia - interruption to blood supply (blockage of a vessel and heart failure)
Histiocytic hypoxia - inability to utilise oxygen in cells due to disabled OxP enzymes (cyanide poisoning)
Immune system damaging damaging body’s cells
Hypersensitivity reactions -host tissue is injured secondary to an overly vigorous
immune reaction, e.g., urticaria (= hives)
Autoimmune reactions -immune system fails to distinguish self from non-self
Toxins
Glucose and salt in hypertonic solutions, high conc of O2, poisons, pollutants, insecticides, herbicides, asbestos, alcohol, Narcotic drugs, medicines
Which cell components are most susceptible to injury
- Cell membranes - Plasma membrane and Organellar membranes
- Nucleus - DNA
- Proteins - Structural (Enzymes)
- Mitochondria - disruption of Oxidative phosphorylation
What is happening at molecular level at hypoxia
Blockage in capillary means cells further along the capillary dont receive oxygenated blood
Mitochondria cant do ETC so no OxP
ATP pump doesn’t work well
So you get:
— sodium pump doesn’t work as well as no ATP, so high Na+ conc, causes influx of Ca2+ + water and flux of K+ ions - all this leads to cellular swelling, ER welling and loss of cell integrity
Calcium conc increase in cells also causes major problems as it activates some fo the protease and nucleases
— Increase in glycolysis for anaerobic respiration could lead to build up of lactate and lactic acid which decreases pH which can cause clumping of nuclear chromatin in the nucleus
What about prolonged hypoxia
At some point the damage can become irreversible
Can lead to complete membrane permeability
Ca flows in
Can’t activate any enzymes leading to detrimental effects
By activation of ATPase (causes decreased ATP), phospholipids (causes decreased phospholipids), protease (causes disruption of PM) and endonucleases (causes nuclear chromatin damage
Cell injury with causes other than hypoxia
Sequence of events for other insults may be different but as the cell has a limited responses to injury, outcome often similar.
Other forms of injury might attack different key structures, e.g., extreme cold (e.g., frostbite) damages membranes initially.
Free radicals also damage membranes primarily.
What are free radicals?
These are reactive oxygen (and nitrogen) species
Single unpaired electron in an outer orbit
3 radicals are of particular biological significance in cells
OH
Free radicals are formed by
UV light - Air pollution - Ionising radioation - Smoking - Metabolism - Inflammation
When are free radicals produced
- Normal metabolic reactions: e.g., oxidative phosphorylation
- Inflammation: oxidative burst of neutrophils
- Radiation: H20 —> 0H.
- Contact with unbound metals within the body: iron (by Fenton reaction) and copper
Free radical damage occurs in haemachromatosis and Wilson
How do free radicals injure cells
If the number of free radicals overwhelms the anti-oxidant system = oxidative imbalance
Most important target are lipids in cell membrane
Cause lipid periodisation, this leads to generation of further free radicals —> auto catalytic chain reaction
Also oxidise proteins, carbohydrates and DNA, These molecules become bent out of shape, broken or cross-linked
How does the body control free radicals
- Anti-oxidant scavengers: donate electrons to the free radical
How else can the cell protect itself against injury
Heat shock proteins - In cell injur
Mechanisms of intracellular accumulations
1) abnormal metabolism
2) alterations in protein folding and transport
3) deficiency of critical enzymes
4) inability to degrade phagocytosed particles
Seen when metabolic processes become deranged
Often occur with sublethalor chronic injury
Can be reversible
Can be harmless or toxic
They can derive from the -
What kind of things can accumulate in cells?
1) water and electrolytes
2) lipids
3) Carbs
4) Proteins
5) pigments